DE2355898A1 - NEW SECONDARY AND TERTIAL SULPHONES - Google Patents

Description

New secondary and tertiary sulfones

The present invention relates to new sulfones, as well as their use in the synthesis, of products from the family Terpenes, and carotenoids.

These new sulfones conform to the general formula

Λ ~ C (CH ₅ ) ~ Q

(D

in which R denotes an optionally substituted alkyl, alkylaryl, arylalkyl or aryl radical.

A represents a saturated or unsaturated, conjugated, or j not conjugated polyenic, functionalized or by Alkyl groups are substituted radical, which has one or more isoprene linkages. If. The number of concatenations is at least equal to 2, A may have a ring on which, if appropriate Alkyl groups and / or functional groups, such as, for example, = 0 or -OH, which can be free or protected, are attached could be. A can also be halogenated and / or comprise the following functional groups:

an alcohol function, the ethers corresponding to this function

409820/1199

or the esters that these with inorganic or organic Forms acids,

a free or protected aldehyde function,

an acid puncture or the derivatives of the acidic function, j such as acid chloride, ester, amide, Titrile,

a function -SR ¹ or -SO ₂ R '> for which R' denotes an alkyl, alkylaryl, aryl or arylalkyl radical.

Q can be a hydrogen atom or a saturated or unsaturated, conjugated or non-conjugated polyenic, functionalized or by alkyl groups, especially methyl groups, substituted cabbage env / a ss he st off rest mean. Q can also contain a ring to which optionally Alkyl groups and / or functional groups, such as, for example, = 0 or -OH, which can be free or protected, be bound can. Q can also be halogenated and / or the following functional groups have:

an alcohol function, the ethers corresponding to this puncture or the esters it forms with inorganic or organic acids,

a free or protected aldehyde function,

an acid puncture or the derivatives of acid puncture, such as for example acid chloride, esters, amides, nitrile,

a puncture -SR ¹ or -SO ₂ R ¹ »for which R ^{1 is} an alkyl, alkylaryl, aryl or arylalkyl radical.

The compounds of formula I for which Q is a hydrogen atom means and therefore the formula

^A -? ": ^CH 3 (id

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are referred to below as secondary sulfones to indicate that the sulfone function is from a secondary carbon atom is carried, and the compounds of the formula I for which Q is a radical other than a hydrogen atom, are called tertiary sulfones.

The manufacture of the 'secondary' SuIfone can be done by implementing of an alcohol of the formula A - CHOH -CH ^ with an alkali sulfinaf be made in the presence of an inorganic or organic acid. This is called AcH. The reaction can be represented by the following scheme:

A - CHOH - CH + RSO ₂ M ... , AcH j A-CH - SOgR + AcM + 11 ^ 0

j In this scheme, M means an alkali metal. You can do this! Reaction also to an isomer of the secondary alcohol ACHOHCH ₇ J j that can be converted into this in the course of the reaction. ._... ·.
i

It is possible to carry out the reaction in a solvent such as a hydrocarbon, an alcohol or an ether ■■. The temperature can range from -2o ° C to -HOO ⁰ C! vary and in most cases is of the order of magnitude; from +10 "to + 4O ⁰ C

The compounds of the formula II can also be prepared from a halide j of the formula A-CHX-CH-z, in which A has the abovementioned meaning ; and X represents a halogen atom. and an alkali sulf produce inat. The reaction can be represented by the following scheme:

A-CHX-CH ₃ + RSO ₂ M ^. . A-CH- SOgR + XM-

The reaction is preferably carried out in a solvent or a mixture of solvents, such as a hydrocarbon9 ZoBo hexane, benzene and toluene, an alcohol ₉ ζ »Β» methanol or ethanol, a linear or cyclic ether ₉

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$ 235,589

! e.g. ethyl ether, dioxane or tetrahydrofuran or also dimethyl

' sulfoxide, dimethylformamide, dimethyl acetamide, or hexamethylohosphoric acid amide. The reaction proceeds easily under mild conditions, and the separation of the sulfone sought presents no difficulty, since the alkali metal halide formed during the reaction can be removed from the reaction mass by simple washing with water.

Among those used for the preparation of the sulfones of the formula I. Secondary alcohols can be called the secondary alcohols obtained by selective hydrogenation of commercially available ketones, such as Methylheptenone, ionons, irons, and pseudojonons will. ■.

The halides are produced by halogenation of secondary alcohols A - CHOH - CH-z or their isomers with a phosphorus trihalide, Thionyl chloride or phosgene prepared by the usual methods for carrying out this reaction.

The preparation of the tertiary sulfones of the formula I, for which Q is a radical as defined above, can - starting of the secondary sulfones of the formula II - are made with a halide of the formula Q'X, in which Q · the same Has the same meaning as Q with the exception of a hydrogen atom and X represents a halogen atom in the presence of a basic one Implemented means. This reaction can be represented schematically as follows:

? ^H A i " ³ :

A - Q® + XQ ¹ -} A ~ C ~ Q + X

! I.

SO ₂ R SO ₂ R

In this scheme, X is preferably chlorine or bromine.

The "basic agent should have sufficient activity ₉ anionize zn to the secondary Su'lfon and binding of the hastes Q ^aiii! These zn ο One can enable or inorganic

use organic compounds such as the hydroxides, alcoholates, hydrides or amides of alkali metals. The organometallic compounds such as organozinc compounds, organolithium compounds and organomagnesium compounds are also suitable. This can Anionisierungsmittel ί alone or together with other basic agents, for the Neutralization new ■ the hydrohalic acid formed are determined -, Pall the anionizing agent 'used' alone, νer-; v / ends, the amount used should be sufficient to: ensure this neutralization. This amount is also a punctuation of the working methods and the reactivity of the reaction process. against this basic agent. From these various NEN reasons it may be advantageous to introduce into the reaction a minor amount anionisierendes agent and to add another basic agent, over the reaction products j are less sensitive and the gebil- for neutralization; deten hydrohalic acid is sufficient.

j The reaction is conducted at temperatures which betra- from -100 ° C to +150 ⁰ C ί depending on the type of used and products obtained; gen can be carried out.

For the reaction to proceed properly, it is advantageous to work in an organic solvent that is a hydrocarbon : substance, such as hexane, benzene or toluene., a protic Solvent such as methanol, ethanol or ethylene glycol, or a linear or cyclic ether one Monoalcohol or a diol, such as ethyl ether, dioxane or tetrahydrofuran, may be. Other solvents, such as dimethylformamide, dimethylacetamide, dimethyl sulfoxide, N-methylpyrrolidone and hexamethylphosphoric triamide, can also be suitable.

If you have a secondary suIfon with a product that has two Has halogen atoms on two different carbon atoms, condenses, a tertiary disulfone is obtained. A special pail of this reaction consists in 1,4-dichlorobutene- (2) or

409820/1199

T3 & 5898

1,4-dibromobutene- (2) to be used. The disulfones, which after the Reaction scheme

CII ₃ SO ₂ R.

j 2 A - CII (CH ₅ ) - SO ₂ R + ClCl ^ CE = CH - CI ^ Cl ^ ^^^ ₊

(HI)

'obtained have a particular interest in the syn- ' -. thesis of carotenoids.

; The tertiary sulfones can be subjected to a reducing desulfonation treatment, compounds of the formula A - CH (CEU) Q ^{1 then being} obtained. They can also be treated with an inorganic or organic basic agent such as an alkali hydroxide, an alkali carbonate or an alkali alcoholate. The products obtained then have an ethylenic double bond according to A - C (CEU) = Q ¹ . The basic desulfonation of the disulfones shown in the reaction scheme in 'leads to compounds of the formula

^ - ^ V ^A (IT)

the tail-to-tail isoprene concatenation of carotenoids ι have.

ι Depending on the chosen desulfonation route, acyclic! sinsäure or cyclic terpene products such as myrcene, G-eraniol, citronellol, citral, geranic acid and esters thereof, Parnesal, parnesol and its esters, ferns and their \ derivatives Axerophthen and its lower or higher Isoprenologe and the functional derivatives of the same row, ; "in particular retinal and its acetals, vitamin A, its ethers and esters, vitamin Α-acid, its esters and its nitrile, '< other function el Ie derivatives of retinin, such as • 4-oxoretinal, the apocarotinals and the corresponding Alcohols ₅

as well as their ethers and esters and the apocarotenoic acids and their ! Derivatives. Carotenoid compounds containing 40 carbon ; have atoms or more can also be produced <'

One can, inter alia, name the various carotenes such as β-carotene, i-carotene, lycopene, astacin, canthaxanthin, zeaxanthin, isozeaxanthin and, in general, the xanthophyl compounds corresponding to these different carotenes where sulfones are used that have the linkage (X) can also be used to produce compounds whose molecule contains a saturated or unsaturated polyisoprene linkage, such as vitamin E or vitamins K ₁ and K ₂ *

j The desulfonation can be carried out with the isolating from the reaction medium ten suIfon or in this medium. As well as i is the chosen procedure, there is a release of an alkali sulfinate or a sulfinic acid, which occurs during manufacture

^; of the starting sulfone can be reused, so that the synthesis of the polyisoprene compounds, which proceeds via these sulfones, consumes practically no alkali metal sulfinate. ^f

^: The following examples serve to further explain the invention. ^Ä

' Example 1

26 g of 8- / 2 ", 6,6-trimethylcyclojhexen- (1) -yl7" -6-methyl-octatrien- (3,5,7) -ol- (2) are placed in a 1 liter flask. with a degree of purity of 90 percent, 31.8 g of sodium phenyl sulfinate and

3
440 cm of acetic acid. The mixture is left with stirring at room temperature for 16 hours and then the excess acetic acid is evaporated off under the vacuum of a vane pump. - The pulpy residue obtained is taken up in water and then four times with each

3 ■

125 cm ether extracted »The combined ether layers are

■ 3

with water and then with 2oo cm of an aqueous 10 percent Washed sodium bicarbonate solution and dried over magnesium sulfate ο By evaporating the ether one gets 33. g one! pulpy product in which ,, mau by IT-Spsktrograpliie

0/1

90 percent of a product determined, the i _n t _he UV spectrography

! an absorption maximum at 340 nm (E ₁ '° = 732) in ethanol aufj ι cm

j points and the formula -

is equivalent to. The degree of conversion is 100 percent and the yield 87 percent,. .

! Example 2 "" ·.

The procedure is as in the previous example and 25.8 g of ß-ionol and 41 g of sodium phenyl sulfinate are reacted in 450 cm of acetic acid. The mixture is left to react for 16 hours, then the acetic acid and I 3 are removed

! takes the reaction mass concentrated in this way in 500 cm of ethyl ether ι · *
ι and 500 cm of distilled water. The aqueous I layer is separated off and extracted twice with 250 cm of ethyl ether each time. From the combined ether layers treated as above, 33 g of a pale yellow viscous liquid are isolated, in which 26.4 g of the compound of the formula

determined and identified. This product lies after recrystallization from isopropyl ether in the form of a crystallized white product of P = 50 ° C. The yield is 62.4 percent.

Example 3

Su T a solution of ₅ 12 g Uatrium p-toluenesulfinate in 40 cm Sssigsäure sets a solution of 5, 88.g Pseudojonol in 40 om ⁵ to acetic acid. The reaction is allowed to proceed with stirring for 16 hours. The vinegar is evaporated

'S

amazed fleii lüülsstaai tn sinaai S-smisGla τοώ 5 € ss';! ©.-s

! and 25 cm 'of ethyl ether.

After decanting, washing the aqueous layer twice with 20 cm of ether each and treatment of the combined ether layers under the conditions of Example 1, a viscous yellow liquid j is obtained in which one can see by TJV and KMR spectrography a product of the formula

certainly. The degree of conversion is 100 percent and the yield is 93.5 percent. \

Example 4 ■ ■

A mixture of 2.34 g of 8- ^ 2 ", 6,6-trimethylcyclohexene ( 1) -yl7-6-methyloctatriene- (3 ', 5,7) -ol- (2) with

3 3.88 g sodium p-methoxyphenyl sulfinate in 45 cm acetic acid react. Bach removal of the acetic acid turns the residue into

3 - 3 ··

a mixture of 100 cm V / water and 100 cm ethyl ether added. Decant, extract the aqueous layer twice

3 ··
each with 25 cm of ether and treated the combined ether layers as in the previous examples. This gives 2.9 g of a pure product, identified and determined by UY and NMR spectrography, that of the formula

u · CJI. OCH 2 6 4 3

is equivalent to. The sodium pmethoxyphenyl sulfinate used as the starting substance becomes from p-methoxyphenylsulfonyl chloride according to that described in Acta chemica Scandinavica ■ JJ7 »page 380, 1963 Process made.

Example 5 -

3
In a 500 cm flask equipped with a dropping funnel

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• ζ

', one brings 4.86 g of sodium methylate to 120 cm of tetrahydro-

i furan, then lowers the temperature to -10 ° C and continues

! 15.32 g of 8- ^, 6,6-trimethylcyclohexen- (1) -yl7-6-methyl-2-phenyl-

I sulfonyloctatrien- (3 ₅ 5,7) (in Example 1 prepared product

I -k

: duct) in solution in 70 cm of tetrahydrofuran. Then you let ': a solution of 4> 92 g 1,4-dibromobutene- (2) in 30 cm tetrahydro-

pour in furan and leave to react for 2 hours at -10 C and then for one hour at room temperature. Removal of wax from: two-thirds of the amount of the solvent under the vacuum ^egg: ner vane pump; the reaction mass is poured into a mixture

■ z -z.

'of 400 cm of water and 2 00 cm of ethyl ether, decant and extract the aqueous layer four times with 50 cm ether each time. Treatment of the combined ether layers (washing with water / water, drying, concentration) yields 16.22 g of a crude oil, that contains 87 percent of a product, 'identified by UV and UMR spectrography is identified. Its formula is:

^! The degree of conversion is 100 percent and the yield is 90 percent.
The product purified by recrystallization in isopropyl ether

; dükt has a melting point of 140 to 145 ⁰ C. It shows in UY spectrography in ethanolic solution an absorption

, maximum at 308 nm (E] '° = 780).

ι win

The l _i ii ~ dibromobutene- (2) v / urde according to the method described in the Journal of Chemical: Society, page 241, "1949" by slow: addition of bromine in solution in carbon tetrachloride to butadiene

in solution in the same solvent while maintaining the tempe-! temperature at -20 ⁰ O produced.

Example 6

Production of ß-carotene. A mixture is brought in which consists of 0.587 g of the sulphone previously prepared, 10 cm of hexane and 336 mg

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Potassium tert-butoxide ordered to 60 ° C. Hold the heating for 40 minutes, then let it cool. The reaction mass is poured into 200 cm of a mixture of ChDxroform / water ■ '■ "(50/50). ■ · ■ \

The separated organic layer is washed with water until neutral, dried and then concentrated. Is isolated so 0,465g of crude beta-carotene, which comprises at the UY spectrography an absorption maximum E £ _Λ of 1250 at 454 nm; The degree of conversion is 100 percent and the yield is 87 percent.

Example 7 \

3 g of the disulfone prepared in the above example are added

• z "- -

in 131 cm of chloroform and puts 5 g of potassium periodate in solution

• 2 · 3

sung in 32.5 cm of water and 11 cm of ethyl alcohol and then

3
12.7 cm of a 1 percent solution of iodine in chloroform. It is allowed to react at room temperature (24 ⁰ G) for 65 hours

3 yaw and pour the reaction mass into a mixture of 100 cm

■ 5
Water and 40 cm of chloroform. The separated organic layer is neutralized with an aqueous sodium bicarbonate solution, washed with water until neutral, dried over magnesium sulfate and concentrated. A brown solid product is obtained in which a compound of the formula

ι identified.

Two characteristic bands in UV spectrography (itha- : nol):

j at 303 by ■ E} jf _m »378

; at 258 mn EI f _m - 388 j

'The Umv / andlungsgraa is 100 Ecοκeat _$ dl © yield §1

ti- '

820/11

Example 8

Manufacture of canthaxanthin. 0.424 g of the disulfone prepared in the previous example with 0.448 mg of potassium tert-butoxide in 20 cm of hexane and 10 cm of dimethyl sulfoxide are added. The temperature is increased to '50 ⁰ C and stirred for 2 hours under stirring, the reaction cooling reagieren.Nach

3 3

put it in a mixture of 80 cm of water and 30 cm of chloroform poured. The separated aqueous layer is extracted with chloroform and the combined chloroform layers are as previously treated. This isolates 0.500 g of product in which the canthaxanthin is identified by UV spectrography.

Example 9

To a solution of 4.5 g of that prepared according to Example 1

3
Sulphone in 210 cm of chloroform is put into 8.25 g of potassium periodate

3 3

in solution in 52.5 cm of water and 1.7 cm of ethyl alcohol and then

21 cm of a 1 percent solution of iodine in chloroform. The mixture is left to react for 42 hours at room temperature (24 ° C.) and

3 3

then pour the mixture into 200 cm of water and 100 cm of chloroform. It is decanted, neutralized with an aqueous sodium bicarbonate solution and washed with water. The Piltrat will be three

3 - ■
times extracted with 50 cm chloroform. 5.2 g of a viscous oil in which a product of the formula is isolated by NMR spectroscopy is isolated from the combined chloroform layers, dried over magnesium sulfate, filtered and concentrated

30, φ

identified and determined. The conversion rate is 100 pro sent and the yield 82 percent.

Example 1Q - '^;

; ui sirien ait an ascending. Cooler and a drip funnel iivijgest & 'twben pistons are brought to the state

3.2 g of the sulfone prepared according to Example 2 and Io cm. Tetrahydrofuran. After dissolving compartment is cooled to -4.0 ⁰ C and then sets 3.66 g of potassium tert-butylate in 5 cm of tetrahydrofuran. 4 »6 g of 1,4-dibrompentene- (2) in solution in 5 cm of tetrahydrofuran are added to the red-colored ^{reaction mixture, which has been cooled to -5O 0 G.} The addition takes 45 minutes and is carried out with stirring. After 5 hours you pour that

3 3

Reaction mixture in 25 cm ice water, water and 25 cm ethyl ether. The aqueous layer is decanted and extracted twice with

'3

each 20 cm of ether. The ether layers are combined, washed with water, dried, filtered and concentrated. So you get 7 _? 3 g of a dark orange viscous product in which - 'by NMR spectrography, 4.3 g of a compound of the formula

identified and determined.

The degree of conversion is 100 percent and the yield 94.5 percent.

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Claims (6)

Claims sulfones of the general formula : SO ₂ R in the R is an optionally substituted alkyl, alkylaryl, Arylalkyl or aryl radical, A is a saturated or unsaturated, conjugated or non-conjugated polyenic, functionalized or alkyl group-substituted radical which has one or more isoprene linkages, where, if the number of linkages is at least gMch 2, A can contain a ring on which optionally alkyl groups and / or functional groups, such as = 0 or -OH, which can be free or protected, can be bonded, and where A can also be halogenated and / or can carry the following functional groups an alcohol function, the ethers corresponding to this function or the esters which these with inorganic or organic Acids "forms, a free or protected aldehyde function, an acidic puncture or the derivatives of the acidic function _s such as acid chloride, esters, amides, uritrile, a function. -SR ^{ _{or -SO 2} R ¹ J for which R ^{1 is} an alkyl, alkylaryl, aryl or arylalkyl radical, and Q is a hydrogen atom or a saturated or unsaturated, conjugated or non-conjugated polyenic, functionalized or substituted by alkyl groups, in particular methyl groups Can mean the remainder, with Q. also containing a complaint 409820/1199 th, on which optionally alkyl groups and / or functional Groups, like = 0 or --0H, that are free or protected. can, can be bonded, and where Q can also be halogenated and / or can have the following func tional groups: an alcohol function, the ethers corresponding to this puncture or the esters that this forms with inorganic or organic acids, a free or protected aldehyde function, an acidic puncture or the derivatives of the acidic function ,, like Acid chloride, ester, amide, uritrile, a puncture -SR 'or -SO ₂ R ¹ J for which E' denotes an alkyl, alkylaryl, aryl or arylalkyl radical. 2.. 2-arylsulfonyl-6,1.0-dimethylundecatriene- (3,5,9). 3. 4- / 2 \ 6, ö-trimethylcyclohexen- (1) -yl / ^r -2-arylsulfonyl-: butene- (3) ^; 4. 8- ^, 6,6-trimethylcyclohexen- (1) -yl7-6-methyl-2-aryl-; sulfonyloctatriene- (3,5,7) 5. 8- ^ 2 ", 6, o-Irimethylcyclohexen- (1) -ylj-ö-arylsulfonyl-6 methyl-2-bromoctadiene- (3.7) · 6. 8 - ^ ", 6,6-trimethyl-4-oxocyclohexen- (1) -y2 / 7'-6-methyl-2-. Arylsulfonyloctatriene- (3 ₅ 5,7) · ; 7. 13,13'-diarylsulfonyl-β-carotenes. 8.13.13 ^! -Diarylsulfonyl-canthaxanthine ο j 9 ° Method for the production of suIfonen according to claim 1 _S = characterized “that if the symbol Q represents a hydrogen atom, an alkali metal -a ^ jfisulfinat of the formula RSO ₂ M, in which E has the meaning given above, and M represents an alkali metal, with a secondary alcohol of the formula A - GHOH - CH ₇ , in which A has the meaning given above, or with an isomer of this alcohol which can be converted into this alcohol during the reaction, the reaction being carried out in the presence of an inorganic or organic acid, or an alkali metal sulfinate of the formula RSOoM with a halide of Formula A - CHX - CH, in which A has the meaning given above and X represents a halogen atom, reacts or j if Q denotes an organic radical as defined above, a halide of the formula Q ¹ X, in which Q * has the same meaning as Q with the exception of a hydrogen atom and X denotes a halogen atom b., with a sulfon of the formula A-CH- CH, I J SO ₂ R in which A and R have the meanings given above, converts, the reaction being carried out in the presence of a basic agent. 10 · Use of sulfons of the formula A-CH- CH,
I °
SO ₂ R in which A and R have the meanings given above, for Production of terpene compounds, Garοtinοidverbindungen, ß-carotene and canthaxanthin. 4Ό9820 / 1Τ99